Valenza Carmine, Nicolò Eleonora, Mongillo Marta, Trapani Dario, Katrini Jalissa, Boldrini Laura, Boscolo Bielo Luca, Castellano Grazia, Guidi Lorenzo, Pellizzari Gloria, Villa Jacopo, Derio Silvia, Lapresa Mariateresa, Gigli Federica, Parma Gabriella, Omodeo Salè Emanuela, Derenzini Enrico, Curigliano Giuseppe, Colombo Nicoletta
Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy.
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Oncologist. 2025 Jul 4;30(7). doi: 10.1093/oncolo/oyae330.
Patients with a germline BRCA pathogenic variant (gBRCA-PV) and advanced high grade ovarian carcinoma (aHGOC) experience higher hematologic adverse events (HAEs) when receiving platinum salts and ionizing radiations, compared to non-carriers, due to a possible higher susceptibility of the hemopoietic stem cells to DNA targeting agents. However, the incidence of PARP inhibitor (PARPi)-related HAEs according to the gBRCA-PV status is currently unknown.
We conducted a single-center retrospective cohort study to describe the occurrence of HAEs in patients with aHGOC receiving ≥8 weeks of maintenance PARPi in any line of therapy, comparing gBRCA-PVs carriers to non-carriers. HAEs were manually identified by searching the patients' electronic medical records and classified by CTCAE v5.0. The main endpoint was the incidence rate of any HAE (ie, anaemia, neutropenia, or thrombocytopenia) of grade 2 or more (G ≥ 2).
One hundred and sixty-six patients were included; 95 (57%) had a gBRCA-PV. In total, 162 incident cases of G ≥ 2 HAEs were reported over 255.3 person-years. The incidence rates of G ≥ 2 HAEs were 1003/1000 person-years in gBRCA-PV carriers and 993/1000 person-years in non-carriers. No difference in the incidence rate of G ≥ 2 HAEs emerged comparing gBRCA-PV carriers to non-carriers (crude-incidence rate ratio [IRR]: 1.01; 95% CI: 0.72, 1.43; P = .96), even after adjusting for the type of PARPi (Mantel-Haenszel IRR: 0.99; 95% CI: 0.67, 1.46).
Patients with aHGOC and a gBRCA-PV do not experience higher PARPi-related HAEs compared to non-gBRCA-PV carriers, unlike platinum salt-related HAEs.
与非携带者相比，携带生殖系BRCA致病变异（gBRCA-PV）的晚期高级别卵巢癌（aHGOC）患者在接受铂盐和电离辐射时，由于造血干细胞对DNA靶向药物的易感性可能更高，会经历更高的血液学不良事件（HAEs）。然而，目前尚不清楚根据gBRCA-PV状态，PARP抑制剂（PARPi）相关HAEs的发生率。
我们进行了一项单中心回顾性队列研究，以描述接受任何一线治疗且维持PARPi治疗≥8周的aHGOC患者中HAEs的发生情况，比较gBRCA-PV携带者和非携带者。通过查阅患者电子病历手动识别HAEs，并根据CTCAE v5.0进行分类。主要终点是2级或更高级别（G≥2）的任何HAE（即贫血、中性粒细胞减少或血小板减少）的发生率。
纳入166例患者；95例（57%）有gBRCA-PV。在255.3人年中，共报告了162例G≥2的HAE事件。gBRCA-PV携带者中G≥2的HAEs发生率为1003/1000人年，非携带者为993/1000人年。比较gBRCA-PV携带者和非携带者，G≥2的HAEs发生率没有差异（粗发生率比[IRR]：1.01；95%CI：0.72，1.43；P = 0.96），即使在调整PARPi类型后（Mantel-Haenszel IRR：0.99；95%CI：0.67，1.46）。
与铂盐相关的HAEs不同，aHGOC和gBRCA-PV患者与非gBRCA-PV携带者相比，PARPi相关的HAEs发生率并不更高。
